"A Computational Framework for Predicting Cell-Specific Nucleo-Cytoskel" by Madison Leigh Goldfeldt

Publication Date

5-2024

Date of Final Oral Examination (Defense)

12-11-2023

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Mechanical Engineering

Department Filter

Mechanical and Biomechanical Engineering

Department

Mechanical and Biomedical Engineering

Supervisory Committee Chair

Gunes Uzer, Ph.D.

Supervisory Committee Member

Clare Fitzpatrick, Ph.D.

Supervisory Committee Member

Aykut Satici, Ph.D.

Abstract

Understanding the influence of mechanical forces on cell function and fate is crucial in unraveling the intricate mechanisms that govern cellular behavior. The cytoskeleton, a dynamic network of protein filaments, plays a pivotal role in sensing and transmitting mechanical cues within cells. The nucleus relies on cytoskeletal mechanical input through nuclear envelope adaptor proteins to sense external stimuli and respond by regulating intra-nuclear chromatin organization. This research provides a means for examining the interplay between mechanical forces and the cytoskeleton in regulating various cellular processes, including cell adhesion, migration, division, and differentiation. Through studying and simulating the cellular response to mechanical forces, this research aims to bridge the gap between mechanics and biology, uncovering the interrelation between physical forces and biochemical signaling. The developed computational framework reliably reconstructs nucleo-cytoskeletal morphology and computes cytoskeletal forces on the nuclear surface via finite element (FE) analyses. Utilizing this method, we found that cytoskeletal force was sensitive to changes in nuclear Young’s modulus and volume. Our cell specific models further confirm apical stress fibers’ role as critical load-carrying components, deforming the nuclei by 46.93% - 51.67% and matching target intact profiles with 2.19%-13.20% accuracy. In summary, our computational framework provides an important tool to probe nucleo-cytoskeletal Factin forces in cells and may shed light on fundamental questions in nuclear mechanotransduction and diseases where cytoskeletal force generation is impaired.

DOI

https://doi.org/10.18122/td.2168.boisestate

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